Systematic Analysis of Efflux Pump-Mediated Antiseptic Resistance in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Suggests a Need for Greater Antiseptic Stewardship

ABSTRACT Staphylococcus aureus-associated infections can be difficult to treat due to multidrug resistance. Thus, infection prevention is critical. Cationic antiseptics, such as chlorhexidine (CHX) and benzalkonium chloride (BKC), are liberally used in health care and community settings to prevent i...

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Autores principales:	Patrick T. LaBreck, Audrey C. Bochi-Layec, Joshua Stanbro, Gina Dabbah-Krancher, Mark P. Simons, D. Scott Merrell
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Staphylococcus aureus antimicrobial agents benzalkonium chloride chlorhexidine efflux pumps Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/61162b0ee3ee47f49b289e7a2abc9690
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spelling	oai:doaj.org-article:61162b0ee3ee47f49b289e7a2abc96902021-11-15T15:27:52ZSystematic Analysis of Efflux Pump-Mediated Antiseptic Resistance in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Suggests a Need for Greater Antiseptic Stewardship10.1128/mSphere.00959-192379-5042https://doaj.org/article/61162b0ee3ee47f49b289e7a2abc96902020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00959-19https://doaj.org/toc/2379-5042ABSTRACT Staphylococcus aureus-associated infections can be difficult to treat due to multidrug resistance. Thus, infection prevention is critical. Cationic antiseptics, such as chlorhexidine (CHX) and benzalkonium chloride (BKC), are liberally used in health care and community settings to prevent infection. However, increased administration of antiseptics has selected for S. aureus strains that show reduced susceptibilities to cationic antiseptics. This increased resistance has been associated with carriage of specific efflux pumps (QacA, QacC, and NorA). Since prior published studies focused on different strains and on strains carrying only a single efflux gene, the relative importance of these various systems to antiseptic resistance is difficult to ascertain. To overcome this, we engineered a collection of isogenic S. aureus strains that harbored norA, qacA, and qacC, individually or in combination. MIC assays showed that qacA was associated with increased resistance to CHX, cetrimide (CT), and BKC, qacC was associated with resistance to CT and BKC, and norA was necessary for basal-level resistance to the majority of tested antiseptics. When all three pumps were present in a single strain, an additive effect was observed in the MIC for CT. Transcriptional analysis revealed that expression of qacA and norA was significantly induced following exposure to BKC. Alarmingly, in a strain carrying qacA and norA, preexposure to BKC increased CHX tolerance. Overall, our results reveal increased antiseptic resistance in strains carrying multiple efflux pumps and indicate that preexposure to BKC, which is found in numerous daily-use products, can increase CHX tolerance. IMPORTANCE S. aureus remains a significant cause of disease within hospitals and communities. To reduce the burden of S. aureus infections, antiseptics are ubiquitously used in our daily lives. Furthermore, many antiseptic compounds are dual purpose and are found in household products. The increased abundance of antiseptic compounds has selected for S. aureus strains that carry efflux pumps that increase resistance to antiseptic compounds; however, the effect of carrying multiple pumps within S. aureus is unclear. We demonstrated that an isogenic strain carrying multiple efflux pumps had an additive resistance phenotype to cetrimide. Moreover, in a strain carrying qacA and norA, increased chlorhexidine tolerance was observed after the strain was preexposed to subinhibitory concentrations of a different common-use antiseptic. Taken together, our findings demonstrate cooperation between antiseptic resistance efflux pumps and suggest that their protective phenotype may be exacerbated by priming with subinhibitory concentrations of household antiseptics.Patrick T. LaBreckAudrey C. Bochi-LayecJoshua StanbroGina Dabbah-KrancherMark P. SimonsD. Scott MerrellAmerican Society for MicrobiologyarticleStaphylococcus aureusantimicrobial agentsbenzalkonium chloridechlorhexidineefflux pumpsMicrobiologyQR1-502ENmSphere, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Staphylococcus aureus antimicrobial agents benzalkonium chloride chlorhexidine efflux pumps Microbiology QR1-502
spellingShingle	Staphylococcus aureus antimicrobial agents benzalkonium chloride chlorhexidine efflux pumps Microbiology QR1-502 Patrick T. LaBreck Audrey C. Bochi-Layec Joshua Stanbro Gina Dabbah-Krancher Mark P. Simons D. Scott Merrell Systematic Analysis of Efflux Pump-Mediated Antiseptic Resistance in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Suggests a Need for Greater Antiseptic Stewardship
description	ABSTRACT Staphylococcus aureus-associated infections can be difficult to treat due to multidrug resistance. Thus, infection prevention is critical. Cationic antiseptics, such as chlorhexidine (CHX) and benzalkonium chloride (BKC), are liberally used in health care and community settings to prevent infection. However, increased administration of antiseptics has selected for S. aureus strains that show reduced susceptibilities to cationic antiseptics. This increased resistance has been associated with carriage of specific efflux pumps (QacA, QacC, and NorA). Since prior published studies focused on different strains and on strains carrying only a single efflux gene, the relative importance of these various systems to antiseptic resistance is difficult to ascertain. To overcome this, we engineered a collection of isogenic S. aureus strains that harbored norA, qacA, and qacC, individually or in combination. MIC assays showed that qacA was associated with increased resistance to CHX, cetrimide (CT), and BKC, qacC was associated with resistance to CT and BKC, and norA was necessary for basal-level resistance to the majority of tested antiseptics. When all three pumps were present in a single strain, an additive effect was observed in the MIC for CT. Transcriptional analysis revealed that expression of qacA and norA was significantly induced following exposure to BKC. Alarmingly, in a strain carrying qacA and norA, preexposure to BKC increased CHX tolerance. Overall, our results reveal increased antiseptic resistance in strains carrying multiple efflux pumps and indicate that preexposure to BKC, which is found in numerous daily-use products, can increase CHX tolerance. IMPORTANCE S. aureus remains a significant cause of disease within hospitals and communities. To reduce the burden of S. aureus infections, antiseptics are ubiquitously used in our daily lives. Furthermore, many antiseptic compounds are dual purpose and are found in household products. The increased abundance of antiseptic compounds has selected for S. aureus strains that carry efflux pumps that increase resistance to antiseptic compounds; however, the effect of carrying multiple pumps within S. aureus is unclear. We demonstrated that an isogenic strain carrying multiple efflux pumps had an additive resistance phenotype to cetrimide. Moreover, in a strain carrying qacA and norA, increased chlorhexidine tolerance was observed after the strain was preexposed to subinhibitory concentrations of a different common-use antiseptic. Taken together, our findings demonstrate cooperation between antiseptic resistance efflux pumps and suggest that their protective phenotype may be exacerbated by priming with subinhibitory concentrations of household antiseptics.
format	article
author	Patrick T. LaBreck Audrey C. Bochi-Layec Joshua Stanbro Gina Dabbah-Krancher Mark P. Simons D. Scott Merrell
author_facet	Patrick T. LaBreck Audrey C. Bochi-Layec Joshua Stanbro Gina Dabbah-Krancher Mark P. Simons D. Scott Merrell
author_sort	Patrick T. LaBreck
title	Systematic Analysis of Efflux Pump-Mediated Antiseptic Resistance in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Suggests a Need for Greater Antiseptic Stewardship
title_short	Systematic Analysis of Efflux Pump-Mediated Antiseptic Resistance in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Suggests a Need for Greater Antiseptic Stewardship
title_full	Systematic Analysis of Efflux Pump-Mediated Antiseptic Resistance in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Suggests a Need for Greater Antiseptic Stewardship
title_fullStr	Systematic Analysis of Efflux Pump-Mediated Antiseptic Resistance in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Suggests a Need for Greater Antiseptic Stewardship
title_full_unstemmed	Systematic Analysis of Efflux Pump-Mediated Antiseptic Resistance in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Suggests a Need for Greater Antiseptic Stewardship
title_sort	systematic analysis of efflux pump-mediated antiseptic resistance in <named-content content-type="genus-species">staphylococcus aureus</named-content> suggests a need for greater antiseptic stewardship
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/61162b0ee3ee47f49b289e7a2abc9690
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Systematic Analysis of Efflux Pump-Mediated Antiseptic Resistance in <named-content content-type="genus-species">Staphylococcus aureus</named-content> Suggests a Need for Greater Antiseptic Stewardship

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